Targeting Neuroinflammation as a Contributing Pathology in Alzheimer's Disease Dementia and Related Dementias

Alzheimer's disease (AD) dementia is a devastating illness with no cure. Treatments targeting known pathologic hallmarks of AD, such as amyloid-beta (AB), in symptomatic individuals have proved largely fruitless so other potential disease targets warrant exploration. Neuroinflammation has interesting possible associations with AD dementia and may contribute to AD dementia in different ways among different individuals. Previous PET neuroinflammation data are not entirely consistent and new methods of PET imaging and studies with larger cohorts are needed to further investigate the role of neuroinflammation in AD dementia and the utility of PET as a biomarker. This project seeks to test new PET neuroinflammation imaging methods in unimpaired, mildly impaired, AD dementia, and mild cognitively impaired and dementia with Lewy bodies (DLB) individuals with biomarker-identified brain pathology to help address these gaps in knowledge in the field.

Inclusion criteria

• Males or females 60 years of age or older.
• Meet the requirements for one of the five groups (CU A-, CU A+, MCI A+, AD A+, MCI-LB or DLB).
• Neurologic evaluation procedures with testing in the MCSA, ADRC, Longitudinal Imaging Biomarkers of Prodromal and Overt DLB studies or Mayo Clinic Behavioral Neurology Practice. Must have had or plan to have at least 2 testing sessions.
• All participants must have or plan to have an amyloid PiB PET scan and MRI brain scan within approximately 6 months of the first ER176 PET/CT scan. Participants undergoing an optional additional ER176 scan are preferred, but not required, to have or plan to have an amyloid PiB PET scan and MRI brain scan within approximately 6 months of the second ER176 PET/CT scan.
• Capacity to sign consent or have a legally authorized representative to sign the consent.

Exclusion criteria

• Participants unable to lie down without moving for 20 minutes.
• Women who are pregnant or cannot stop breast feeding for 24 hours.
• Actively taking daily anti-inflammatory medications (NSAIDs, corticosteroids, etc.) except for a small control group.
• Generalized inflammatory condition and treatment with immunosuppressive, corticoid/glucocorticoid, steroidal or non-steroidal anti-inflammatory medication within 2 weeks of scanning (only acute medication use as an exclusion so as to limit medication interaction but preserve possible chronic systemic inflammation interaction).
• Standard safety exclusionary criteria for MRI such as metallic foreign bodies, pacemaker, etc., since the quantitative PET data analysis is based on anatomic criteria that are established uniquely for each subject by registration to his/her MRI.